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Polymer physics and structural organization of chromosomes in mammalian genomes.
Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the various loci, important to the genome functionality, are derived with high accuracy and their molecular determinants identified by the theory; for instance, the Sox9 locus self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Finally, the model predictions on the effects of mutations on folding are tested against experimental data. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.